Tissue comprises organized cellular groups that are attached to an extracellular matrix and are surrounded by a network of blood vessels. Fibrosis is an abnormal accumulation of a collagen matrix following injury or inflammation which alters the structure and function of various tissues. Irrespective of location, the major pathology of fibrosis involves an excessive deposition of a collagen matrix which replaces the normal tissue at that site. Progressive fibrosis in the kidney, liver, lung, heart, bone or bone marrow, and skin is a major cause of death and suffering. See, e.g., Border, et al., New Engl. J. Med. 331:1286 (1994).
Development of fibrosis has been linked to the overexpression and over-production of TGF-.beta. in numerous tissues and fibrotic disease states (see Border et al., N Engl J Med 1994, pp. 1286-92).